Field of the Invention
This invention is directed to methods and compositions for treating active dermatoses (e.g., dermatitis, psoriasis and eczema).
Specifically, in one aspect, this invention is directed to methods for forming in situ a coherent polymeric film over the active dermatosis by topical application of a polymerizable cyanoacrylate ester composition to the affected skin areas and subsequent polymerization of the composition. The coherent polymeric film acts as an occlusion layer over the affected skin areas. Preferably, the polymerizable cyanoacrylate ester composition comprises a corticosteroid which is released from the polymeric film in therapeutically effective amount.
In another aspect, this invention is directed to cyanoacrylate ester compositions comprising polymerizable cyanoacrylate esters and a therapeutically effective amounts of at least one corticosteroid. Optionally, these compositions further comprise an antimicrobial agent to inhibit microbial infections under the polymeric film.
References
The following publications, patents and patent applications are cited in this application as superscript numbers:
1 Askill, et al., U.S. patent application Ser. No. 08/912,678, for Methods for Draping Surgical Incision Sites, filed Aug. 18, 1997 PA1 2 Remington's Pharmaceutical Sciences, 17th Edition, 1985 PA1 3 Hawkins, et al., Surgical Adhesive Compositions, U.S. Pat. No. 3,591,676, issued Jul. 6, 1971 PA1 4 Halpern, et al., Adhesive for Living Tissue, U.S. Pat. No. 3,667,472, issued Jun. 6, 1972 PA1 5 Rabinowitz, et al., Method of Surgically Bonding Tissue Together, U.S. Pat. No. 3,527,224, issued Sep. 8, 1970 PA1 6 Kronenthal, et al., Surgical Adhesives, U.S. Pat. No. 3,995,641, issued Dec. 7, 1976 PA1 7 Davydov, et al., Medical Adhesive, U.S. Pat. No. 4,035,334, issued Jul. 12, 1977 PA1 8 Waniczek, et al., Stabilized Cyanoacrylate Adhesives Containing Bis-Trialkylsilyl Esters of Sulfuric Acid, U.S. Pat. No. 4,650,826, issued Mar. 17, 1987 PA1 9 McIntire, et al., U.S. Pat. No. 3,654,239, for Process for the Preparation of Poly(.alpha.-Cyanoacrylates), issued Apr. 4, 1972 PA1 10 O'Sullivan, et al., U.S. Pat. No. 4,038,345, for High Viscosity Cyanoacrylate Adhesive Compositions, and Process for Their Preparation, issued Jul. 26, 1977 PA1 11 Greff, et al., U.S. Pat. No. 5,684,042 for Cyanoacrylate Compositions Comprising an Antimicrobial Agent to issue Nov. 4, 1997 PA1 12 Greff et al., U.S. Pat. No. 5,480,935, for Cyanoacrylate Adhesive Compositions issued on Jan. 2, 1996 PA1 13 Blum, et al., In vitro Determination of the Antimicrobial Properties of Two Cyanoacrylate Preparations, J. Dent. Res., 54(3):500-503 (1975) PA1 (a) applying to the topical surface of the dermatosis a polymerizable cyanoacrylate ester composition; PA1 (b) polymerizing the cyanoacrylate ester composition in situ on said surface so as to form a coherent polymeric film over the dermatosis. PA1 (a) a polymerizable cyanoacrylate ester; and PA1 (b) a therapeutically effective amount of a corticosteroid. PA1 alkenyl of 2 to 10 carbon atoms, PA1 cycloalkyl groups of from 5 to 8 carbon atoms, phenyl, PA1 2-ethoxyethyl, PA1 3-methoxybutyl, PA1 and a substituent of the formula: ##STR2## wherein each R' is independently selected from the group consisting of: hydrogen and methyl, and PA1 R" is selected from the group consisting of:
All of the above publications, patent applications and patents are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent application or patent was specifically and individually indicated to be incorporated by reference in its entirety.
State of the Art
Treatment regimens for many mammalian skin diseases such as dermatosis include the topical application of a corticosteroid onto the diseased skin. The corticosteroid is typically formulated as an ointment, cream, lotion, solution, etc., and topical application to the skin is conducted once or more per day until the disease condition abates.
Some dermatoses are characterized by a greatly accelerated rate of epidermal turnover. Normally, skin regeneration is a controlled process where keratinocytes of the epidermal layer regenerate, differentiate and are pushed to the skin surface. There, the keratinocytes cornify, die and are shed. The natural regeneration process generally takes about 28 to 30 days.
In contrast to natural skin regeneration, psoriasis is a chronic disease characterized by epidermal hyperplasia and a greatly accelerated rate of epidermal turnover (hyperproliferation of keratinocytes). The lesions are characteristically red, slightly raised and scaly and can be quite unsightly. The lesions may be localized or generalized and may cause discomfort such as burning and itching.
Topical application of corticosteroids to skin areas undergoing active dermatosis leads to reduced skin inflammation (reduced reddening of the skin) as well as reduced skin itching. By reducing the inflammatory process, corticosteroids can permit healing to occur.
Nevertheless, several problems arise in such treatment regimens. First, direct physical contact of clothing with inflamed irritated skin can cause painful abrasions. Second, after application of the corticosteroid composition, any contact of the treated skin with clothing, water (washing), etc. results in removal of at least a portion of the topically applied corticosteroid thereby lessening the therapeutic effect. Third, in certain skin disease conditions such as psoriasis, the preferred treatment regimen includes occlusion of the skin for prolonged periods of time. Occlusion, however, can lead to unsightly bandages/wraps which may interfere with normal activities particularly where the disease condition is on the arms or legs. Moreover, bathing and other water activities become problematic, at best, when bandages/wraps are placed on the patient. In the case of other dermatoses where bandages are not required, the topical ointments or creams can wash or rub off onto and stain clothing, or in the case of overnight use, bedding.
This invention is directed, in part, to the discovery that in situ formation of a cyanoacrylate polymeric film over the diseased skin overcomes many of the prior art problems recited above. Preferably, the cyanoacrylate composition further comprises a corticosteroid which additionally provides incremental advantages heretofore not achieved by conventional occlusion wraps. For example, the cyanoacrylate polymer is waterproof and forms an occlusion over the diseased skin which permits the patient to bath, wash, swim, etc. without concern that such activities would interfere with the occlusion wrap. Still another advantage is the formation of an appropriately configured wrap without the need to modify the dimensions provided with commercial wraps. Still further, the methods and compositions of this invention result in wraps which mold directly to the multiple contours of the intended occlusion sites. In any event, the corticosteroid is released from the film over time to deliver a therapeutically effective amount of this drug to the skin.